Functional magnetic resonance imaging (fMRI) has permitted measurement of local changes in cerebral blood volume, flow, and oxygenation within localized cortical areas of the brain in response to task activation. Due to its superior spatial and temporal resolution in addition to being non-invasive, fMRI is fast becoming the method of choice for studying systems level neuroscience of the human brain. fMRI is currently being used extensively to characterize and map sensory, motor, and cognitive function in healthy subjects as well as patients. The objective of this proposal is to develop statistical processing strategies to quantify differences in the fMRI response in cortical regions of the brain in subjects with Alzheimer's Disease (AD) compared with age- and gender - matched controls and to test the hypothesis that statistically significant differences in the fMRI task-induced response, including both signal magnitudes and spatial extent of activation, exist in AD subjects compared with controls. As steps in testing this hypothesis three specific aims will be achieved: (1) reduction of noise arising from head motion, (2) development of non-parametric statistical methods suitable for this problem, and (3) analysis of shapes of task-activated regions coupled with analysis of anatomic variability. Data from several subjects together with data from several age- and gender-matched controls has already been acquired and will be used to test analysis methods to be developed here.A rigorous statistical processing strategy that in addition to quantifying differences in fMR images between AD and matched controls will permit determination of the relative contribution from the various sources that result in differences in task activation response is proposed in this project. This may provide a basis for the use of fMRl in diagnosis and severity of AD. Differences due to different tasks from the same subject group can also be studied using the methods proposed in this project.